Neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's chorea, and Machado-Joseph disease, occurs at a rate of one person in 10 thousand to 30 thousand for each disease. In Japan alone, the existence of more than 100 thousand patients (one person per 1,200) has been confirmed (Ministry of Welfare; Journal of Health and Welfare Statistics, 1996). Therefore, much effort has been made on the research of preventative and therapeutic methods (Borlongan, C. V., Koutouzis, T. K., Sanberg, P. R., Neurosci. Biobehav. Rev. 21, 289-93 (1997); Parnetti, L., Senin, U., Mecocci, P., The way forward. Drugs. 53, 752-68 (1997); Pasinetti, G. M., Neurobiol. Aging. 17, 707-16 (1996)). Studies have found that neurodegenerative diseases share a common phenotype. That is, it has been confirmed that the aggregation and accumulation of aberrant proteins, which have distinctive characteristics such as extended glutamine chain, abnormal conformation, resistance to proteases, β-sheet structure, etc., cause the formation of vacuoles and cell death cells (Kakizuka, A., Trends Genet. 14, 396-402 (1998)).
However, the causal matter that is involved in the induction of aggregation and accumulation of such aberrant proteins, which then cause the formation of vacuoles and cell death, is yet to be identified, thereby delaying the research and development of remedies and prophylactics for neurodegenerative diseases.
The inventors of the present application have, through assiduous work, succeeded in identifying the factor that induces the phenotype common to such neurodegenerative diseases, and revealed that the factor is a valosin-containing protein (VCP)
VCP, an AAA (ATPase Associated with various cellular Activities) super family protein existing generally in organisms ranging from eucaryotic cells to humans, has a weak ATPase activity and has been considered to be involved in various cell functions, particularly signal transduction (Muller, J M., Meyer, H. H., Ruhrberg, C., Stamp, G. W., Warren, G., Shima, D. T., J. Biol. Chem. , 274, 10154-10162 (1999); Zhang, L., Ashendel, C. L., Becker, G. W., Morre, D. J., J. Cell Biol., 127, 1871-1883 (1994)). However, VCP was not known to be a factor that induces neurodegenerative diseases by binding with aberrant proteins.
On the basis of this new finding, it is expected that by establishing a method for screening substances that inhibiting the binding of VPC and the aberrant protein, substances that are commonly effective as therapeutic or prophylactic drugs for a specific disease, as well as for a series of neurodegenerative diseases may be obtained.
The invention of the present application was made in view of the above-described situation, and its object is to solve the problems of the prior art and to provide a method for screening substances useful as effective components in prophylactic or therapeutic drugs for neurodegenerative diseases.